P664: REAL-WORLD ANALYSIS OF MUTATION CHARACTERISTICS AND CLINICAL OUTCOMES IN 343 CHRONIC MYELOID LEUKEMIA PATIENTS WITH BCR::ABL KINASE DOMAIN MUTATIONS
Authors: Shiwei Hu, Dijiong Wu, Weiying Feng, Lili Chen, Lihong Cao, Xiaoqiong Zhu, Xiudi Yang, Jingjing Zhu, Huafeng Wang, Dan Chen, Hongyan Tong, Ying Lu, Honglan Qian, Yi Wang, Jie Jin, Jian Huang
Journal: HemaSphere (2023)

Background: BCR::ABL kinase domain (KD) mutation is highly associated with poor prognosis of chronic myeloid leukemia (CML). However, it remains unclear what the mutation characteristics and clinical outcomes of CML patients (pts) with BCR::ABL mutations are in the real world. Aims: To assess the mutation characteristics and clinical outcomes related to times, stages and types of mutations. Methods: A total of 343 CML pts with BCR::ABL KD mutations were collected from 28 hematooncology centers in China between 2010 and 2022 (ChiCTR2200061208). Relevant clinical data were collected for comparative analysis. Results: 484 mutations of 45 different types were identified in 343 pts, of which T315I, Y253H, E255K/V, F359V/C/I, G250E and F317L were listed top six (FigureA, B). Pts with T315I were younger (P=0.048), had shorter time from CML diagnosis to mutation detection (P=0.005), a higher proportion to be detected in BP (P=0.004) and a higher proportion of ≥2 lines porior TKIs (P<0.001). Pts with F359V/C/I had lower WBC (P=0.043) and a higher proportion to be detected in CP (P=0.008). Pts received Imatinib had intricate mutation types, while pts received Dasatinib had more monotonous mutation types (Figure C). Further analysis found that pts received first- or second- or third-line Dasatinib (P=0.019, P<0.001, P=0.047) tended to had T315I, third-line Nilotinib to E255K/V (P=0.028), second-line Nilotinib to F359V/C/I (P<0.001) and second-line Dasatinib to F317L (P<0.001). With a median follow-up of 80 months, median OS and PFS was 90 and 60 months (Figure E). The 3-year cumulative incidences of achieving CCyR, MMR, MR4.0 and MR4.5 were 68.3%, 65.0%, 58.8% and 52.8%, respectively. The probabilities of sustained CCyR, MMR, MR4.0 and MR4.5 at 3 years were 75.9%, 69.2%, 50.9% and 50.6%, respectively (Figure F). There was no statistical significance in the OS and PFS between first and ≥second mutation groups (Figure G). When grouped according to the stages of mutation, median OS was significantly worse in BP (13 months) and AP (65 months) groups than that in CP (158 months) group (P<0.001); this difference was same in the assessment of median PFS in BP (8 months), AP (30 months) and CP (90 months) groups (P<0.001) (Figure H). Of pts with top six mutations, there was statistical difference in OS (P=0.044) and PFS (P=0.014). Pts with T315I had the worst prognosis, followed by pts with E255K/V, F317L, G250E, Y253H and F359V/C/I mutations (Figure I). In the analysis of efficacy of different treatment strategies, T315-mutated pts with HSCT had better OS (P<0.001) and PFS (P=0.003) than Ponatinib and palliative care (pointless TKIs) (Figure J). However, F359V/C/I-mutated pts received HSCT had worse outcomes in PFS than Dasatinib and palliative care (P=0.011). Summary/Conclusion: Dasatinib predisposed pts to T315I and F317L, Nilotinib to E255K/V and F359V/C/I. The stage of mutation had a greater impact on prognosis than times of mutational events. T315I had the worst prognosis and F359V/C/I had a relatively better prognosis. HSCT had a positive effect for T315I-mutated pts and negative effect for F359V/C/I-mutated pts. This research was funded by Key R&D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; Zhejiang Medical Association Clinical Medical Research special fund project, No. 2022ZYC-D09; Key Project of Jinhua Science and Technology Plan, China, No. 2020-3-011. *Correspondence to: Prof Jian Huang, Prof Jie Jin.Keywords: BCR::ABL, Tyrosine kinase inhibitor, Chronic myeloid leukemia